The objectives of this proposal is to study the role of flanking DNA sequences and chromatin configuration in the developmental regulation of gene expression in the mouse. For this purpose, cloned rabbit beta globin genes will be microinjected into the one cell stage mouse embryo. DNA microinjection should allow the efficient transfer and insertion of DNA into mouse embryos without the need for selection and should result in the insertion of DNA into different sites within the mouse genome. After development to term in a surrogate mother, the tissues of the adult mice obtained will be examined for integration and expression of the rabbit beta globin gene. The sites of rabbit beta globin gene integration will be examined, both in terms of its chromatin configuration and the DNA sequences flanking the insert, and will be correlated with the pattern of tissue specificity of rabbit beta globin expression. It is hoped that these observations will allow the construction of an integrated model for understanding the mechanisms operative in the developmental regulation of gene expression. In particular, it is hoped that these studies will lead to some insights as to what is the nature of the involvement of DNA sequences and chromatin structures in this process. It is hoped that this study will contribute in the long run to the understanding of how faulty regulation of gene expression can lead to "dedifferentiation" and uncontrolled growth in tumor cells.